Isolated limb perfusion therapy is routinely used in several centers as a regional adjuvant to the surgical treatment of soft tissue sarcoma. Publiched results suggests a need for more effective drug regimens. Regional adjvant therapy has become increasingly important in the management of soft tissue sarcomas of the extremity. Not only has local recurrence remained a significant problem after definitive surgery and radiation but ther is in addition, renewed interest in attempting limb sparing surgery for tumors that in the past would have required amputation. Despite the fact that systemically administered adriamycin is the single most effective drug for metastatic soft tissue sarcoma, it has not been employed in perfusion because of a reluctance among clinicians to embark upon a clinical program without basic toxcicity snd pharmacologic data of the drug used in the perfusion system. Furthermore, moderate hyperthermia 39-40.5 degrees C is often used in perfusion and the effects of heat on the toxicity and pharmacokinetics of the drug in this system are unknown. We have developed a unique model canine system to obtain basic pharmacokinetic and toxicity data thereby limiting the amount of clinical empiricism when newly developed regimens are used in man. The objectives of the proposed study are to 1) obtain additional data regarding the toxicity and pharmacokinetics and metabolism of adrimycin during normothermic isolation perfusion of canine hind limbs and determine the effects of adding hyperthermia and/or radiation therapy either before or after perfusion on drug disposition and toxicity in this experimental system. We have obtained preliminary information on normothermic perfusion. The general advantage of perfusion therapy is that extremely high concentration of drug can be delivered to the perfused area with no systemic side effects. Another advantage is that the regional adjuvant therapy by perfusion and the definitive surgery can be done during the same anesthetic. In instances where tumors are found by a clinical trial of perfusion to be highly drug sensitive, the need for radiation may be lessened or not needed. In instances where previous radiation has failed, excision and effective perfusion is the obvious choice over amputation.